1. Field of the Invention:
The present invention relates to controlled release dosage forms. Specifically, the present invention provides an improved expandable osmotic layer and an improved expandable osmotic layer coating suspension, both of which better facilitate commercial manufacture of controlled release dosage forms utilizing a coated, expandable osmotic layer.
2. State of the Art:
Controlled release dosage forms created using a coated, expandable osmotic layer are known in the art. For example, U.S. Pat. No. 5,413,572 (“the '572 Patent”), U.S. Pat. No. 5,324,280 (“the '280 Patent”) and U.S. application Ser. No. 09/866,036 (“the '036 Application”), now U.S. Pat. No. 6,419,952, all teach controlled release dosage forms created by coating hard or soft gelatin capsules with an expandable osmotic layer. In general, the controlled release liquid capsules taught in these publications include a capsule that is pre-filled with a liquid active agent formulation, an expandable osmotic layer formed around the pre-filled capsule, a semipermeable layer formed around the expandable osmotic layer, and an exit orifice through which the liquid active agent formulation included in the capsule is delivered as the dosage form operates. As taught in the '036 Application, a baffler layer may be positioned between the capsule and the expandable osmotic layer in order to achieve more consistent and better controlled delivery of the liquid active agent formulation.
In use, the controlled release dosage forms taught in the '572 Patent, the '280 Patent, and the '036 Application draw water from their environment of use through the semipermeable layer and into the expandable osmotic layer. As water is absorbed into the expandable osmotic layer, the expandable osmotic layer expands and compresses the capsule such that the liquid formulation contained therein is expelled through the exit orifice at a controlled rate over a desired period of time. Although the controlled release dosage forms taught in the referenced publications achieve the controlled release of active agent formulations, it has been found that the formulation of the expandable osmotic layer included in these dosage forms creates some difficultly when attempting to produce such dosage forms at a commercial scale. In particular, the expandable osmotic layer formulation taught in the '572 Patent, the '280 Patent, and the '036 Application has proven to be sensitive to processing conditions, exhibiting a tendency to produce cracked osmotic layers if the process conditions are not closely monitored to provide dry process conditions.
The expandable osmotic layer of the controlled release liquid capsules taught in the referenced publications typically includes an osmopolymer, such as sodium carboxy methylcellulose (NaCMC), an osmotic agent, such a NaCl, and a film former, such as hydroxyethylcellulose (NATRASOL®) To coat an intermediate dosage form with an expandable osmotic layer incorporating these constituents, a coating suspension suitable for a spray coating process is typically formulated by mixing the solid constituents included in the expandable osmotic layer into a two solvent system, such as a water and ethanol solvent mixture. Once the coating suspension is formed, the expandable osmotic layer is coated on intermediate dosage forms using, for example, a known spray coating technique. As is well known, spray coating processes generally involve agitating a batch of devices to be coated (in this case, a batch of intermediate dosage forms) while spraying a coating formulation over or around the devices such that, over a period of time, the devices are coated with a material layer of desired thickness. Coating suspensions previously used to coat an expandable osmotic layer included 4.9 wt % NaCMC, 8.1 wt % NaCl, 3.0 wt % NATRASOL®, and 84 wt % solvent mixture, such as, for example a mixture of 62.7 wt % water and 21.3 wt % EtOH solvent. The previously used coating suspensions typically produced expandable osmotic coatings including 30.6 wt % NaCMC, 50.6 wt % NaCl, and 18.8 wt % NATRASOL®. Although coating suspensions according to the previous formulations generally produce osmotic layers of acceptable quality when the spray coating conditions are closely monitored to ensure a dry coating process, under wet processing conditions, such coating suspensions produce an unacceptably high number of coated devices having expandable osmotic layers tat are cracked and, therefore, unsuitable for further processing.
The process sensitivity of the previous coating suspensions and resulting expandable osmotic layers are disadvantageous from at least two standpoints. First, as dosage forms are processed at a commercial scale, it becomes more difficult to precisely control process parameters. Therefore, a coating suspension that provides acceptable material only under particular process conditions is undesirable, because, at a commercial scale, the quality of the material layers produced using such a coating suspension may be unpredictable. Second, wet spray coating processes (i.e., spray coating processes characterized by relatively higher solvent concentrations in the coating environment) are generally recognized as more efficient. Yet in order to produce expandable osmotic layers of a desired level of quality and performance, the previous coating suspensions require that the expandable osmotic layers be coated under dry process conditions. As is easily understood, such a requirement is particularly disadvantageous in a commercial context because it forces the use of a less efficient process and leads to increases in the required process times, the amounts of materials used, and, ultimately, the cost of manufacturing the dosage form.
In order to avoid the potential disadvantages exhibited by the previous coating suspensions and the expandable osmotic layers produced thereby, it would be desirable to provide a coating suspension that is less process sensitive. In doing so, however, the function of the expandable osmotic layer must be considered and preserved. Both the osmotic activity and the expansion capabilities of an expandable osmotic layer included in a controlled release dosage form are essential to the proper function of the device. It would be an improvement in the art, therefore, to provide an expandable osmotic layer and coating suspension that are less sensitive to process conditions, yet do not compromise the function of a controlled release dosage form. Such an expandable osmotic layer and coating suspension would not only allow the coating of the expandable osmotic layer under varying process conditions but would facilitate commercial production of controlled release dosage forms including coated expandable osmotic layers.